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PMID: 10440236 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Calcium-induced stabilization of AU-rich short-lived mRNAs is a common default response.

Gene expression ·Vol. 7 ·No. 4-6 ·1999-00-00 ·Pages 357-65

Klein N, Curatola AM, Schneider RJ

Abstract

The AU-rich element (AUUUA)n, found in the 3' noncoding region of many short-lived cytokine and proto-oncogene mRNAs, is sufficient to specifically target these mRNAs for rapid degradation in mammalian cells. The mechanism by which the AU-rich element promotes rapid mRNA decay is not known. Previous studies have shown that release of intracellular stored calcium by ionophore treatment of thymocytes and mast cells inhibits the rapid turnover of AU-rich interleukin mRNAs. Increased cytoplasmic half-life of interleukin mRNAs was linked to calcium-induced activation of the N-terminal c-Jun kinase. In this report we have characterized the calcium-induced stabilization of AU-rich mRNAs. We show that calcium induces stabilization of mRNAs with canonical AU-rich elements in all cell types tested. These results indicate that short-lived mRNA stabilization by calcium is not unique to immune cells nor interleukin mRNAs, but is a widespread default response that includes generic AU-rich mRNAs. Stabilization is shown to be rapid but transient, and to act without altering nuclear transcription or cytoplasmic translation rates. These data support the view that calcium release likely stabilizes short-lived mRNAs by altering trans-acting decay factors that promote AU-rich mRNA turnover.

MeSH Terms
Adenine/metabolism Animals CHO Cells COS Cells Calcimycin Calcium/metabolism Cell Line, Transformed Cricetinae Cytoplasm Gene Expression Regulation Granulocyte-Macrophage Colony-Stimulating Factor/genetics HeLa Cells Humans Ionophores Protein Biosynthesis Protein Processing, Post-Translational Proto-Oncogene Mas RNA, Messenger/metabolism Uracil/metabolism
Chemicals
Ionophores MAS1 protein, human Proto-Oncogene Mas RNA, Messenger Calcimycin Uracil Granulocyte-Macrophage Colony-Stimulating Factor Adenine Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Klein N
Department of Biochemistry and Microbiology, Kaplan Cancer Center, NYU Medical School, New York, NY 10016, USA.
Curatola A M
Schneider R J
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Article Info
Journal
Gene expression
Abbr.
Gene Expr
ISSN
1052-2166
Published
1999-00-00
Pages
357-65
Language
English
Region
United States
NLM ID
9200651
PMCID
PMC6174662
Subset
IM
Grants
NCI NIH HHS · R01 CA042357 · United States
NIAID NIH HHS · 5T32-AI-107180 · United States
NCI NIH HHS · CA-42357 · United States
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